Mast cells in tumor growth: angiogenesis, tissue remodelling and immune-modulation

Abstract

There is a growing acceptance that tumor-infiltrating myeloid cells play an active role in tumor growth and mast cells are one of the earliest cell types to infiltrate developing tumors. Mast cells accumulate at the boundary between healthy tissues and malignancies and are often found in close association with blood vessels within the tumor microenvironment. They express many pro-angiogenic compounds, and may play an early role in angiogenesis within developing tumors. Mast cells also remodel extracellular matrix during wound healing, and this function is subverted in tumor growth, promoting tumor spread and metastasis. In addition, mast cells modulate immune responses by dampening immune rejection or directing immune cell recruitment, depending on local stimuli. In this review, we focus on key roles for mast cells in angiogenesis, tissue remodelling and immune modulation and highlight recent findings on the integral role that mast cells play in tumor growth. New findings suggest that mast cells may serve as a novel therapeutic target for cancer treatment and that inhibiting mast cell function may lead to tumor regression.

Figure 1. Schematic representation of interactions between mast cells and cells within the tumor microenvironment

Developing tumor cells secrete a number of molecules promoting mast cell recruitment. Within the tumor microenvironment, mast cells release a range of mediators affecting tumor cell survival, as well as remodeling of local tissues and recruitment of immune effector cells. Local cells and infiltrating populations also produce and secrete their own subsets of molecules, creating a complex set of interactions. This figure highlights the cell types and molecules mentioned in this review.

Figure 2. Schematic representation of mast cell functions at different stages in tumor progression, using colon polyp formation as an example

Mast cell infiltration occurs rapidly following tumor initiation. Mast cells accumulate at the boundary between healthy tissue and the tumor and early in tumor growth mast cells play an active role in promoting angiogenesis and tissue remodeling. At later stages, mast cells induce immune suppression, promoting tumor growth or alternatively, recruitment of mature immune effector cells, leading to rejection. Interventions with antibodies recognizing TNFα c-kit, VEGF-A or Ang-1 or the chemical cromolyn induce regression, by blocking mast cell maintenance of the tumor.